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Association of Exercise With Mortality in Adult Survivors of Childhood Cancer

Educational Objective
To determine the association between vigorous exercise or a change in exercise and mortality in adult survivors of childhood cancer.
1 Credit CME
Key Points

Question  Is vigorous exercise and change in exercise associated with a reduction in mortality in adult survivors of childhood cancer?

Findings  In this cohort analysis using a questionnaire after a median follow-up of 10 years among 15 450 adult survivors of childhood cancer, there was a significant inverse association across quartiles of exercise and all-cause mortality after adjustment for chronic health conditions and treatment exposures. Increased exercise over 8 years was associated with a 40% reduction in all-cause mortality rate compared with maintenance of low exercise.

Meaning  Vigorous exercise in early adulthood and increased exercise over 8 years is associated with lower risk of mortality in adult survivors of childhood cancer.

Abstract

Importance  Adult survivors of childhood cancer are at excess risk for mortality compared with the general population. Whether exercise attenuates this risk is not known.

Objective  To examine the association between vigorous exercise and change in exercise with mortality in adult survivors of childhood cancer.

Design, Setting, and Participants  Multicenter cohort analysis among 15 450 adult cancer survivors diagnosed before age 21 years from pediatric tertiary hospitals in the United States and Canada between 1970 and 1999 enrolled in the Childhood Cancer Survivor Study, with follow-up through December 31, 2013.

Exposures  Self-reported vigorous exercise in metabolic equivalent task (MET) hours per week. The association between vigorous exercise and change in vigorous exercise and cause-specific mortality was assessed using multivariable piecewise exponential regression analysis to estimate rate ratios.

Main Outcomes and Measures  The primary outcome was all-cause mortality. Secondary end points were cause-specific mortality (recurrence/progression of primary malignant neoplasm and health-related mortality). Outcomes were assessed via the National Death Index.

Results  The 15 450 survivors had a median age at interview of 25.9 years (interquartile range [IQR], 9.5 years) and were 52.8% male. During a median follow-up of 9.6 years (IQR, 15.5 years), 1063 deaths (811 health-related, 120 recurrence/progression of primary cancer, 132 external/unknown causes) were documented. At 15 years, the cumulative incidence of all-cause mortality was 11.7% (95% CI, 10.6%-12.8%) for those who exercised 0 MET-h/wk, 8.6% (95% CI, 7.4%-9.7%) for 3 to 6 MET-h/wk, 7.4% (95% CI, 6.2%-8.6%) for 9 to 12 MET-h/wk, and 8.0% (95% CI, 6.5%-9.5%) for 15 to 21 MET-h/wk (P < .001). There was a significant inverse association across quartiles of exercise and all-cause mortality after adjusting for chronic health conditions and treatment exposures (P = .02 for trend). Among a subset of 5689 survivors, increased exercise (mean [SD], 7.9 [4.4] MET-h/wk) over an 8-year period was associated with a 40% reduction in all-cause mortality rate compared with maintenance of low exercise (rate ratio, 0.60; 95% CI, 0.44-0.82; P = .001).

Conclusions and Relevance  Vigorous exercise in early adulthood and increased exercise over 8 years was associated with lower risk of mortality in adult survivors of childhood cancer.

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Article Information

Accepted for Publication: April 22, 2018.

Corresponding Author: Lee W. Jones, PhD, Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY 10065 (jonesl3@mskcc.org).

Published Online: June 3, 2018. doi:10.1001/jamaoncol.2018.2254

Author Contributions: Drs Scott and Jones had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Scott, Nathan, Gibson, Nilsen, Oeffinger, Ness, Armstrong, Jones.

Acquisition, analysis, or interpretation of data: Scott, Li, Liu, Yasui, Leisenring, Gibson, Amenian, Oeffinger, Ness, Adams, Robison, Armstrong, Jones.

Drafting of the manuscript: Scott, Li, Liu, Adams, Armstrong, Jones.

Critical revision of the manuscript for important intellectual content: Scott, Yasui, Leisenring, Nathan, Gibson, Amenian, Nilsen, Oeffinger, Ness, Adams, Robison, Armstrong, Jones.

Statistical analysis: Li, Liu, Yasui.

Obtained funding: Robison, Armstrong.

Administrative, technical, or material support: Scott, Leisenring, Nilsen, Oeffinger, Adams, Armstrong.

Study supervision: Leisenring.

Conflict of Interest Disclosures: None reported.

Funding/Support: This work was supported by the National Cancer Institute (CA55727, Dr Armstrong. Armstrong, Principal Investigator). Support to St Jude Children’s Research Hospital was also provided by the Cancer Center Support (CORE) grant (CA21765, C. Roberts, Principal Investigator) and the American Lebanese-Syrian Associated Charities (ALSAC). Dr Jones is supported by grants from the National Cancer Institute. Drs Scott, Nilsen, Adams, and Jones are supported by AKTIV Against Cancer, and the Kavli Trust.

Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Meeting Presentation: This work was presented at the American Society of Clinical Oncology Annual Meeting; June 3, 2018; Chicago, Illinois.

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